Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a sub-chronic toxicity study (90 days) by the oral route does not need to be conducted because an appropriate inhalation study is available and inhalation is the most appropriate route of administration as based on the provided thorough and rigorous exposure assessment
other:
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Chloroethane is a gas with an etheral odour.
Physical state at 20°C and 1013 hPa:
gaseous
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 1981 - June 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
no clinical pathology performed; food and water consumption, organ weights (except liver) not determined; no monitoring of exposure conditions (e.g. test concentration)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
other: F344/N
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA)
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: males: 160 - 163 g; females: 124 g
- Housing: individually in stainless steel wire cages (Hazleton Systems, Inc., Aberdeen, MD, USA); no bedding
- Diet (e.g. ad libitum): NIH 07 Rat and Mouse Ration (Zeigler Bros., Inc., Gardners, PA, USA); available ad libitum during non-exposure periods
- Water (e.g. ad libitum): automatic watering system (Edstrom Industries, Waterford, WI, USA); available ad libitum
- Acclimation period: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.7 - 23.3
- Humidity (%): 40 - 65
- Air changes (per hr): 10 during exposure; 20 during non-exposure
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: February 1981 To: June 1981
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapour generation system; the liquid to be vaporized was forced under pressure, at a metered rate, directly from the shipping container into a stainless steel boiler that was maintained at about 32 °C by a controlled-temperature water bath. The vapour was routed through a gas metering valve and a purge/expose valve into a pipe at the chamber inlet, where the vapour was mixed with dilution air entering the chamber.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
5 days/week for 13 weeks
Dose / conc.:
2 500 ppm (nominal)
Remarks:
corresponding to 6596 mg/m³
Dose / conc.:
5 000 ppm (nominal)
Remarks:
corresponding to 13192 mg/m³
Dose / conc.:
10 000 ppm (nominal)
Remarks:
corresponding to 26384 mg/m³
Dose / conc.:
19 000 ppm (nominal)
Remarks:
corresponding to 50130 mg/m³
No. of animals per sex per dose:
10
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: the absence of compound-induced mortality and toxic effects in a subacute study was the basis for selecting 19000 ppm as the highest exposure concentration in the 13-weeks studies.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 3 times per day during exposure

DETAILED CLINICAL OBSERVATIONS: No


BODY WEIGHT: Yes
- Time schedule for examinations: once per week

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: liver weight at necropsy
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (performed on all control and high dose animals)

Tissues examined include: adrenal glands, bone marrow, brain, colon, oesophagus, heart, jejunum, kidneys, larynx, liver, lungs and bronchi, mammary gland, mandibular lymph nodes, nasal cavity, pancreas, parathyroid glands, pituitary gland, prostate/testes or ovaries/uterus, salivary glands, skin, spleen, stomach, thymus, thyroid gland, trachea and urinary bladder.
Statistics:
Survival analyses: estimated by the product-limit procedure of Kaplan and Meier (1985). Statistical analyses for a possible compound-related effect on survival used the method of Cox (1972). All reported P values for the survival analysis are two-sided.

Calculation of incidence: The incidence of neoplastic or non-neoplastic lesions is given as the ratio of the number of animals bearing such lesions at a specific anatomic site to the number of animals in which that site was examined.
Details on results:
CLINICAL SIGNS AND MORTALITY
All rats lived to the end of the study.


BODY WEIGHT AND WEIGHT GAIN
The final mean body weights of rats exposed to 19000 ppm was 8% lower than that of controls for males and 4% lower for females. The limited change (<10%) was not considered to be toxicologically relevant.


ORGAN WEIGHTS
The liver weight to body weight ratio for male rats exposed to 19000 ppm was significantly greater than that for the controls (control: 38.3 +/-1.08; 19000 ppm: 43.5 +/- 0.78; P < 0.01). This is considered to be an adaptive response to the test substance exposure.


GROSS PATHOLOGY/HISTOPATHOLOGY:
No compound-related clinical signs or gross or microscopic pathologic effects were seen.
Key result
Dose descriptor:
NOAEC
Effect level:
50 130 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: non-toxicologically relevant increased relative liver weights; reduced body weight
Critical effects observed:
no
Conclusions:
In a 13-week study, rats were exposed to 0, 2500, 5000, 10000, or 19000 ppm chloroethane. No compound-related deaths occurred in rats. The final mean body weight of rats exposed to 19000 ppm was 8% lower than that of controls for males and 4% lower for females. No compound-related clinical signs or gross or microscopic pathologic effects were seen in rats. The liver weight to body weight ratios for male rats exposed to 19000 ppm were greater than those for controls.
Executive summary:

A thirteen-week study was conducted to evaluate the cumulative toxic effects of repeated whole body inhalation exposure to chloroethane and to determine the exposure concentrations to be used in a 2-year study (National Toxicology Program, 1989). Groups of 10 rats/sex were exposed to air containing chloroethane at target concentrations of 0, 2500, 5000, 10000, or 19000 ppm, 6 hours per day, 5 days per week for 13 weeks (65 exposures). Rats were observed three times per day. Individual animal weights were recorded once per week. At the end of the 13-week study, survivors were killed. A necropsy was performed on all animals. Histologic exams were performed on all control and high dose animals. Tissues examined included: adrenal glands, bone marrow, brain, colon, esophagus, heart, jejunum, kidneys, larynx, liver, lungs and bronchi, mammary gland, mandibular lymph nodes, nasal cavity, pancreas, parathyroid glands, pituitary gland, prostate/testes or ovaries/uterus, salivary glands, skin, spleen, stomach, thymus, thyroid gland, trachea, and urinary bladder; liver weighed at necropsy. Chamber concentrations were determined by GC-FID. All rats lived to the end of the study. The final mean body weights of all exposed groups were lower than those of controls; the final mean body weight of rats exposed to 19000 ppm was 8% lower than that of controls for males and 4% lower for females. No compound-related clinical signs or gross or microscopic pathologic effects were seen. The liver weight to body weight ratio for male rats exposed to 19000 ppm was significantly greater than that for controls. 

Data source

Materials and methods

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion